The etiologic agent of Acquired Immune Deficiency Syndrome (AIDS) is a novel lymphotropic retrovirus termed the Human Immunodeficiency Virus (HIV), which may also be referred to in the literature as LAV, HTLV-III, or ARV. As the spread of HIV reaches pandemic proportions, preventing its transmission has become a paramount concern. To reduce the risk of transfusion-associated HIV infection, hospitals, blood banks, and other users or manufacturers of blood-related products now routinely screen blood donors for the presence of antibodies to HIV. The screening tests typically employ disrupted preparations of purified HIV which have been adsorbed onto a solid surface, such as a microwell or bead. Other screening tests use HIV polypeptides produced by recombinant means, or chemically synthesized peptides which contain immunodominant antigenic regions of HIV. Using such screening tests, the vast majority of the potentially infective units of blood in the donor pool are identified and removed.
Despite the high sensitivity and specificity of the HIV antibody screening tests, a small but significant number of infected blood products still pass undetected into the blood supply. Of primary concern are donors who are infected with HIV at the time they donate blood or plasma but have not yet developed antibodies to the virus. Antibodies may not rise to detectable titers until 3-4 weeks or more after infection. Recent evidence puts the window between time of infection and development of detectable antibody at six weeks to six months. If an infected individual donates blood or plasma during this period, the public blood supply is threatened with an undetected contamination.
To help bridge the gap between the time of initial infection and subsequent seroconversion, a sensitive and specific test for HIV antigens is desirable. Using conventional enzyme immunoassay technology, HIV antigen detection tests have been developed in which polyclonal antibodies to HIV are used to "capture" HIV antigen from a patient or culture sample. The polyclonal antibodies take the form of sera which have been obtained from patients having high antibody titers to HIV, or has been generated in amimal species by immunization. These polyclonal based antigen capture tests have been found to correlate well with the appearance of reverse transcriptase (RT) activity in cell cultures, and they are faster and easier to perform than the RT assay. The use of antisera, however, frequenctly imparts a lack of specificity to the tests, which may yield high background readings, require relatively long incubation periods, and may pose a number of difficulties in the manufacturing process.
Monoclonal antibodies of high affinity and specificity to certain conserved epitopes of HIV could provide a significant improvement over the polyclonal based antigen capture assays described above. While several groups have reported monoclonal antibodies which bind to HIV, the suitability of these antibodies for use in antigen capture assays is unknown. What is needed in the art are monoclonal antibodies specific for conserved antigenic regions of HIV proteins, which antigens are present soon after an individual becomes infected with HIV and, desirably, may be detected with the monoclonal antibodies prior to seroconversion. The present invention fulfills these and other related needs.